If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.


Analytical Chemistry

Smashing drugs illuminates troublesome microcrystals

Unwanted crystals could adversely affect drug stability and shelf life

by Celia Henry Arnaud
May 10, 2018 | A version of this story appeared in Volume 96, Issue 20


Many molecules in the pharmaceutical pipeline suffer from poor aqueous solubility in their crystalline form. To deal with this problem, pharma companies formulate such drugs as amorphous-solid dispersions. However, trace microcrystallinity can negatively affect the stability and shelf life of such formulations.

Unfortunately, current methods for detecting microcrystallinity in drug formulations generally can’t detect it at levels lower than about 1–2%.

Researchers led by Garth J. Simpson of Purdue University now show that triboluminescence—light emitted as a result of mechanical disruption of a crystal—allows them to detect microcrystallinity at levels as low as 0.014% (Anal. Chem. 2018, DOI: 10.1021/acs.analchem.8b01112).

The researchers constructed a system for detecting the triboluminescence. They packed a powder formulation in a 75-mm-long channel in a movable sample stage, struck the powder with a solenoid-driven impactor, which induced triboluminescence, and detected the emitted light. Then they moved the stage to repeat the process with a fresh part of the sample. Their setup allows them to strike a sample 36 times without the impact areas overlapping. The whole process takes about 40 seconds. Purdue Research Foundation has filed a patent application.

As drug developers increasingly turn to metastable amorphous solids they need methods that are capable of detecting and quantifying low levels of crystallinity in drug products, says Steven A. Nowak of AbbVie. The new work shows that triboluminescence “may be well suited for rapid at-line monitoring during manufacturing and possess sufficient detection limits for the determination of low levels of crystals even in amorphous-solid dispersions with low drug loads,” he says.


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.